Mechanisms
Framingham study finds plasma CETP activity has only minimal association with blood pressure change over time (J Hypertens 2011)
Original title: Circulating plasma cholesteryl ester transfer protein activity and blood pressure tracking in the community
Since CETP-inhibitor trials reported an off-target blood-pressure-raising effect, this study examined whether baseline plasma CETP activity predicts longitudinal blood pressure change in one thousand, three hundred and seven Framingham Study participants free of cardiovascular disease, followed over a 4-year interval. Plasma CETP activity was not related to change in diastolic blood pressure and only borderline related to change in systolic blood pressure (P equals 0.09), but was inversely related to change in pulse pressure (beta per SD increment minus 0.71 mmHg, P equals 0.005), with above-median CETP activity associated with a 1 mmHg lower pulse pressure at follow-up (P equals 0.045). The authors conclude that decreasing intrinsic plasma CETP activity is associated with only minimal changes in blood pressure, supporting a compound-specific rather than target-mediated mechanism for the blood pressure effect seen with certain CETP inhibitors.
Original abstract
Objective: Clinical trials using cholesteryl ester transfer protein (CETP) inhibitors to raise high-density lipoprotein cholesterol (HDL-C) concentrations reported an 'off-target' blood pressure (BP) raising effect. We evaluated the relations of baseline plasma CETP activity and longitudinal BP change.
Methods And Results: One thousand, three hundred and seven Framingham Study participants free of cardiovascular disease attending consecutive examinations 4 years apart (mean age 48 years) had baseline plasma CETP activity related to change in BP over the 4-year interval, adjusting for standard risk factors. Systolic BP increased [median +2 mmHg, 95% confidence interval (CI) -16,+23 mmHg], whereas diastolic BP decreased (median -3 mmHg, 95% CI -15,+11 mmHg). Plasma CETP activity was not related to change in diastolic BP, but was inversely related to change in systolic BP that was borderline significant (P=0.09). On multivariable analyses, plasma CETP activity was inversely related to change in pulse pressure (PP; beta per SD increment= -0.71 mmHg, P=0.005). When dichotomized at the median, plasma CETP activity above the median was associated with a 1 mmHg lower PP on follow-up (P=0.045).
Conclusion: Decreasing plasma CETP activity was modestly related to increasing PP on follow-up in our community-based sample, suggesting that inhibition of intrinsic CETP activity itself is likely associated with minimal changes in BP.
blood pressureepidemiologymechanisms
Summary written by cetpinhibition.org from the published abstract; figures as published. Page updated 19 August 2026. Methods.